Deprescribing of antidepressants: development of indicators of high-risk and overprescribing using the RAND/UCLA Appropriateness Method

Background Antidepressants are first-line medications for many psychiatric disorders. However, their widespread long-term use in some indications (e.g., mild depression and insomnia) is concerning. Particularly in older adults with comorbidities and polypharmacy, who are more susceptible to adverse drug reactions, the risks and benefits of treatment should be regularly reviewed. The aim of this consensus process was to identify explicit criteria of potentially inappropriate antidepressant use (indicators) in order to support primary care clinicians in identifying situations, where deprescribing of antidepressants should be considered. Methods We used the RAND/UCLA Appropriateness Method to identify the indicators of high-risk and overprescribing of antidepressants. We combined a structured literature review with a 3-round expert panel, with results discussed in moderated meetings in between rounds. Each of the 282 candidate indicators was scored on a 9-point Likert scale representing the necessity of a critical review of antidepressant continuation (1–3 = not necessary; 4–6 = uncertain; 7–9 = clearly necessary). Experts rated the indicators for the necessity of review, since decisions to deprescribe require considerations of patient risk/benefit balance and preferences. Indicators with a median necessity rating of ≥ 7 without disagreement after 3 rating rounds were accepted. Results The expert panel comprised 2 general practitioners, 2 clinical pharmacologists, 1 gerontopsychiatrist, 2 psychiatrists, and 3 internists/geriatricians (total N = 10). After 3 assessment rounds, there was consensus for 37 indicators of high-risk and 25 indicators of overprescribing, where critical reviews were felt to be necessary. High-risk prescribing indicators included settings posing risks of drug-drug, drug-disease, and drug-age interactions or the occurrence of adverse drug reactions. Indicators with the highest ratings included those suggesting the possibility of cardiovascular risks (QTc prolongation), delirium, gastrointestinal bleeding, and liver injury in specific patient subgroups with additional risk factors. Overprescribing indicators target patients with long treatment durations for depression, anxiety, and insomnia as well as high doses for pain and insomnia. Conclusions Explicit indicators of antidepressant high-risk and overprescribing may be used directly by patients and health care providers, and integrated within clinical decision support tools, in order to improve the overall risk/benefit balance of this commonly prescribed class of prescription drugs. Supplementary Information The online version contains supplementary material available at 10.1186/s12916-024-03397-w.

• TCA (in doses ≥ 50 mg/day) -> this applies to ALL indicators that list TCA: There is limited evidence on the safety of low-dose TCAs (<50 mg/day).Therefore, it was unanimously agreed by the expert panel that a review of their use, particularly at doses ≥50 mg/day, is necessary.
2. Prescribed TCA (in doses ≥ 50 mg/day)1 -and patient has a history of ischemic heart disease.
3. Prescribed >20mg citalopram or >10mg escitalopram daily -and patient is aged ≥65 years (risk of QTc prolongation).4. Prescribed citalopram, escitalopram -and patient has long QT-Syndrome or is at risk of long QT-syndrome (e.g., (advanced) chronic heart failure, ischemic heart disease, myocardial hypertrophy, bradyarrhythmias or an ongoing risk of hypokalaemia 3 ).
3 Ongoing risk of hypokalemia means recurrent hypokalemia despite efforts to improve or without prescription of potassium supplements.
• Woosley RL, Heise CW , Gallo T, Tate J, Woosley D and Romero KA, www.CredibleMeds.org, QTdrugs List, [25.05.2022 12. Prescribed TCA (in doses ≥ 50 mg/day) 1 or trazodone or tranylcypromine 2 -and patient is aged ≥65 years and co-prescribed ≥1 further drug with known blood pressure lowering effect (e.g., α-blockers, β-blockers, nitrates, SGLT-inhibitors, levodopa, antipsychotics) 6 .• Due to the high prevalence of orthostatic hypotension (OH) in geriatric patients, which can lead to falls and fractures, it was agreed upon by the experts that the use of listed antidepressants should be reviewed even in the absence of current OH or dizziness when combined with other drugs known to lower blood pressure.
6 Examples of other drugs with known blood pressure lowering effect are listed in the references in this section.
C. Falls and fall-related injuries • The evidence on antidepressants other than TCAs causing cognitive decline is limited.However, experts agreed to include all anticholinergic antidepressants with ACB Score 2 (opipramol and paroxetine) and ACB Score 3 (tricyclic antidepressants) in the assessment.• Although a higher anticholinergic burden (ACB Score of 4 or ≥5) may be linked to an increased risk of adverse outcomes, including cognitive decline and delirium, the expert panel recommended considering a reduction in ACB score once a score of 3 is reached.This is especially relevant due to the common co-prescription of multiple low-potency anticholinergic medications.• The inclusion of ACB Score thresholds in the indicator was omitted as its use in primary care setting is limited.
19. Prescribed anticholinergic antidepressant opipramol or other TCA (in doses ≥ 50 mg/day) 1 or paroxetine -and patients has a history of delirium and coprescribed ≥1 further drug known to induce delirium (e.g., benzodiazepines, opioids, antihistamines, diuretics) 8 .27. Prescribed SSRI -and patient has at least one risk factor for intracranial bleeding (aged ≥ 65 years, history of stroke, history of dementia) and co-prescribed ≥1 of the following: anticoagulant or antiplatelet.
• Expert panel participants agreed that concurrent treatment with oral anticoagulants and antiplatelet agents should be reserved for exceptional cases due to the significantly increased risk of bleeding.Consequently, the threshold value for indicator Nr. 27 was adjusted to include comedication with at least one of the following: anticoagulant or antiplatelet.• The HAS-BLED score identifies age and history of stroke as risk factors for bleeding, while dementia increases the risk of spontaneous bleeding due to central nervous system parenchymal disturbance.